Molecular docking and radiation dose estimation of PET radiotracers targeting serotonin receptors in depression

Abstract

Major Depressive Disorder (MDD) is a complex psychiatric condition strongly associated with dysregulation in serotonergic neurotransmission, particularly involving the 5-HT_1A and 5-HT_2A receptor subtypes. Positron Emission Tomography (PET) radiotracers targeting these receptors provide a non-invasive method for investigating neurobiological mechanisms of depression. In this study, six ¹⁸F-labeled PET radiotracers were evaluated using an integrated computational approach combining molecular docking, pharmacokinetic and ADMET prediction, and internal radiation dosimetry. Molecular docking was performed using AutoDock Vina via Webina 1.0.5, with receptor structures retrieved from the Protein Data Bank (PDB IDs: 7E2X for 5-HT_1A; 6A93 for 5-HT_2A). ADMET properties were assessed using SwissADME, pkCSM, and ADMETmesh. Radiation dose estimation was conducted using IDAC-Dose 2.1 based on ICRP 133 reference phantoms. Results indicate that Mefway demonstrates the most balanced overall profile for 5-HT_1A imaging, while Cimbi-36 shows superior performance for 5-HT_2A imaging. All tracers remained within acceptable diagnostic dose limits. These findings highlight the importance of multi-parameter computational evaluation in PET radiotracer development.